Adenosine 3'5' monophosphate (cyclic AMP) and guanosine 3' 5' monophosphate (cGMP) and the enzyme systems regulating their synthesis or degradation have been implicated in controlling many biological processes including erythropoiesis. Polycythemic mice will be used in an attempt to evaluate relationships between these nucleotides, the renal erythropoietic factor (REF), and erythropoietin (ESF). Various nucleotides including cyclic AMP will be tested for erythropoietic activity, and the antibody to erythropoietin (anti-ESF) will be used in an effort to test whether the action of the nucleotide involves ESF. Dose response relationships between erythropoiesis and AMP, ADP, ATP, and cyclic AMP will be evaluated. The levels of these nucleotides will be assessed in marrow, kidney and blood during hypoxia and at various intervals following administration of cobalt, norepinephrine and angiotensin. The role of renal protein kinase in regulating erythropoiesis will be tested by using erythropoietically active drugs such as cobalt and testing the production of such a kinase. This kinase will be purified and characterized with respect to its action on the kidney REF which is very likely based on our preliminary results with cobalt. A possible role for erythrocytic protein kinases in the activation of kidney REF will also be tested. The effects of erythropoietically active drugs on renal adenyl cyclase and cyclic nucleotide phosphodiesterase will be studied. Experimentally produced chronic glomerulonephritis will provide an invaluable tool to assess the relationships between cyclic nucleotides, REF, ESF, protein kinases and the chronic anemia of renal disease.